We plan to carry out a systematic search for chelating agents which can be used in the treatment of chronic and acute cadmium intoxication. The relative ability of five types of known and yuet-to-be synthesized chelating agents to enhance the excretion of aged deposits of cadmium from the mouse/rat will be determined with the goal of decreasing the renal cadmium levels. Subsequently, the best of these compounds will be used in studies on rodents to determine if the reduction in the cadmium content of the kidney they provide is accompanied by improvements in the typical parameters used to measure the kidney function as well as an improvement in the histopathology of the kidney. The kidney function tests which we plan to use are blood urea nitrogen and the presence of the enzyme lysozyme in the urine. The histopathology will concentrate on the presence of renal tubular degeneration. The chelating agents which we plan to use in this study are compounds of firm binding capacity for cadmium in low inherent toxicity. They include (l) 2,3-dimercaptopropane-1-sulfonate, a compound with which we have already obtained some enhancement of cadmium excretion from aged deposits, and some related dithiols, (2) Polyuethyleneamines (such as pentaethylenehexamine), (3) Water soluble cryptates in which the central cryptate structures are of a type which have already been shown to bind cadmium firmly when present in lipid (rather than water) soluble structures, (4) three N-acylated d,l, penicillamines, and (5) Acylated glutathiones. We also plan to carry out a comprehensive screening of about thirty chelating agents (including those above) for efficacy as antidotes for acute cadmium intoxication.